Radioisotope generator

ABSTRACT

The invention relates to a device for producing a fluid containing a radioactive constituent, the device comprising: a shielded chamber ( 5 ) within which is located an isotope container ( 6 ) housing a radioactive isotope ( 7 ), the shielded chamber including first and second fluid connections ( 12,13 ) to opposing ends of the isotope container and a fluid conduit ( 14,15 ) extending from each of the first and second fluid connections to a fluid inlet ( 16 ) and a fluid outlet ( 17 ) respectively characterised in that the fluid inlet comprises a single spike ( 22 ) having a substantially circular cross-section, the spike being adapted to penetrate the rubber seal of a vial and the spike having two bores, the first bore extending from a first aperture adjacent the tip of the spike to a fluid connection with the fluid conduit and the second bore extending from a second, separate aperture in the spike to a filtering air inlet.

The present invention relates to a radioisotope generator of the typecommonly used to generate radioisotopes such as metastabletechnetium-99m (^(99m)Tc).

The diagnosis and/or treatment of disease in nuclear medicine constituteone of the major applications of short-lived radioisotopes. It isestimated that in nuclear medicine over 90% of the diagnostic proceduresperformed worldwide annually use ^(99m)Tc labelledradio-pharmaceuticals. Given the short half-life ofradio-pharmaceuticals, it is helpful to have the facility to generatesuitable radioisotopes on site. Accordingly, the adoption of portablehospital/clinic size ^(99m)Tc generators has greatly increased over theyears. Portable radioisotope generators are used to obtain ashorter-lived daughter radioisotope which is the product of radioactivedecay of a longer-lived parent radioisotope, usually adsorbed on a bedin an ion exchange column. Conventionally, the radioisotope generatorincludes shielding around the ion exchange column containing the parentradioisotope along with means for eluting the daughter radioisotope fromthe column with an eluate, such as saline solution. In use, the eluateis passed through the ion exchange column and the daughter radioisotopeis collected in solution with the eluate, to be used as required.

In the case of ^(99m)Tc, this radioisotope is the principle product ofthe radioactive decay of ⁹⁹Mo. Within the generator, conventionally the⁹⁹Mo is adsorbed on a bed of aluminium oxide and decays to generate^(99m)Tc. As the ^(99m)Tc has a relatively short half-life itestablishes a transient equilibrium within the ion exchange column afterapproximately twenty-four hours. Accordingly, the ^(99m)Tc can be eluteddaily from the ion exchange column by flushing a solution of chlorideions, i.e. sterile saline solution through the ion exchange column. Thisprompts an ion exchange reaction, in which the chloride ions displace^(99m)Tc but not ⁹⁹Mo.

In the case of radio-pharmaceuticals, it is highly desirable for theradioisotope generation process to be performed under aseptic conditionsi.e. there should be no ingress of bacteria into the generator.Moreover, due to the fact that the isotope used in the ion exchangecolumn of the generator is radioactive, and is thereby extremelyhazardous if not handled in the correct manner, the radioisotopegeneration process also should be performed under radiologically safeconditions. Therefore, current radioisotope generators are constructedas closed units with fluid inlet and outlet ports providing externalfluid connections to the inner ion exchange column.

U.S. Pat. No. 3,564,256 describes a radioisotope generator in which theion exchange column is in a cylindrical holder which is located withintwo box-shaped elements that are in turn located within appropriateradiation shielding. The holder is closed by rubber plugs at both ends,and the box-shaped elements have passages opposite each of the rubberplugs in which respective needles are located. At the outermost ends ofthe needles quick-coupling members are provided to enable a syringevessel containing a saline solution to be connected to one of theneedles and to enable a collection vessel to be connected to the otherof the two needles. This document acknowledges that as the two syringesform a closed system there is no need for air to be withdrawn or added.

U.S. Pat. No. 4,387,303 describes a radioisotope generator in which airis introduced to the eluate conduit via a branched pipe so that thehollow spike used to delivery the eluate to be collected has a singlebore as the air is introduced into the fluid upstream.

U.S. Pat. No. 4,801,047 describes a dispensing device for a radioisotopegenerator in which the vial containing the saline solution that will beused to flush out the desired radioisotope from the ion exchange column,is mounted in a carrier that is moveable relative to the hollow needleused to pierce the seal of the vial and to extract the saline solution.The drawings of this document clearly illustrate two separate spacedapart hollow needles one to deliver air and one to collect fluid. Thedispensing device is intended to penetrate an elastic stopper and sopresents the problem that any rotational movement of the eluantcontainer will result in tearing of the stopper which in turn destroysthe aseptic environment through the uncontrolled introduction of airinto the system. A similar dual needle system is illustrated in U.S.Pat. No. 5,109,160.

Although piercing devices are known that employ a single spike with twochannels such as that illustrated in U.S. Pat. No. 4,211,588 suchpiercing devices have been restricted in their application in general tointravenous systems.

The present invention seeks to provide a radioisotope generator that issimple in construction but which ensures the necessary degree ofsterility and radiological protection is maintained during use.

In accordance with the present invention, there is provided a device forproducing a fluid containing a radioactive constituent, the devicecomprising: a shielded chamber within which is located an isotopecontainer housing a radioactive isotope, the shielded chamber includingfirst and second fluid connections to opposing ends of the isotopecontainer and a fluid conduit extending from each of the first andsecond fluid connections to a fluid inlet and a fluid outletrespectively characterised in that the fluid inlet comprises a singlespike having a substantially circular cross-section, the spike beingadapted to penetrate the rubber seal of a vial and the spike having twobores, the first bore extending from a first aperture adjacent the tipof the spike to a fluid connection with the fluid conduit and the secondbore extending from a second, separate aperture in the spike to afiltering air inlet.

Thus, with the present invention rotational movement of a vialpenetrated by the spike would not result in tearing of the rubber sealin a manner that would result in the ingress of unfiltered air. Thus,this construction of radioisotope generator ensures that the asepticconditions of the generator are maintained during use.

An embodiment of the present invention will now be described, by way ofexample only, with reference to the accompanying drawings, in which:

FIG. 1 illustrates a radioisotope generator having fluid connections tothe ion exchange column in accordance with the present invention; and

FIG. 2 is an enlarged cross-section of the fluid inlet of the isotopegenerator of FIG. 1.

FIG. 1 illustrates a radioisotope generator 1 comprising an outercontainer 2, a top plate 3 which is sealingly secured to the outercontainer 2, and a separate top cover 4 which is secured to the outercontainer 2 over the top plate 3. Inside the outer container 2 an innershielded container 5, providing shielding against radiation, is locatedwhich is preferably, but not exclusively, made from either lead or adepleted uranium core within a stainless steel shell. The shieldedcontainer 5 surrounds a tube 6 containing an ion exchange column 7. Theion exchange column 7 preferably consists of a mixture of aluminium andsilica, onto which molybdenum in the form of its radioactive isotope,⁹⁹Mo is adsorbed. The tube 6 containing the ion exchange column hasfrangible rubber seals 8 and 9 at opposing ends 10 and 11 which, asillustrated, when in use are pierced by respective hollow needles 12 and13.

Each of the hollow needles 12 and 13 is in fluid communication with arespective fluid conduit 14, 15 that are in turn in fluid communicationrespectively with an eluent inlet 16 and an eluate outlet 17. The fluidconduits 14, 15 are preferably flexible plastics tubing. The tubing 14,extending from the hollow needle 12, passes through a channel in acontainer plug 18, that closes the upper opening 19 to the shieldedcontainer 5, and then extends from the container plug 18 to the eluentinlet 16. The tubing 15, extending from the hollow needle 13, passesthrough a channel in the shielded container 5 to the eluate outlet 17.The inner shielded container 5 is smaller than the outer container 2 andso there is a free space 20 within the outer container 2 above theshielded container 5. This free space 20 accommodates part of the tubing14, 15 extending from the hollow needles to the eluent inlet and eluateoutlet as the lengths of the tubing 14, 15 are both much greater thanthe minimum length required to connect the hollow needles 12, 13 withthe respective eluent inlet 16 and eluate outlet 17.

The top plate 5 of the radioisotope generator 1 has a pair of apertures21 through which respective eluent inlet and outlet components project.The eluent inlet and eluate outlet components are each hollow spikes 22though in the case of the inlet component the hollow spike has twoholes, one for the passage of fluid and one that is connected to afiltered air inlet. This is more clearly illustrated in FIG. 2 and shallbe described in greater detail below. The hollow spike 22 consists of anelongate, generally cylindrical, spike body 23 and an annular retainingplate 24 which is attached to or is moulded as a single part with oneend of the spike body 23. The opposing end of the spike body 23 isshaped to a point and has an aperture communicating with the interior ofthe spike body adjacent the point. This pointed end of the spike body 23is shaped so that it is capable of piercing a sealing membrane of thetype commonly found with sample vials. The annular retaining plate 24forms a skirt projecting outwardly from the spike body 23 and may becontinuous around the spike body or discontinuous in the form of aplurality of discrete projections.

The top cover 4 of the radioisotope generator 1 also includes a pair ofapertures 25 arranged so as to align with the apertures 21 in the topplate 3 and shaped to allow through passage of the spike body 23. Thus,each of the hollow spikes 22 is arranged to be held and supported by itsannular retaining plate 24 by component supports 26 provided on theinside of the top plate 3 whilst the hollow spike body 23 projectsthrough the apertures in both the top plate 3 and the top cover 4 to theexterior of the outer container 2. Each one of the apertures 25 in thetop cover 4 is located at the bottom of a well 27 that is shaped toreceive and support either an isotope collection vial or a saline supplyvial. Thus, both vials are housed outside of the outer container 2 andare not exposed to radiation from the ion exchange column 7.

In order to supply the ion exchange column with the chloride ionsrequired for elution of the radioisotope, saline solution is drawnthrough the ion exchange column 7, by establishing a pressuredifferential across the ion exchange column. This is accomplished byconnecting a saline supply vial to the eluent inlet 16 which is in fluidcommunication with the top end 10 of the ion exchange column 7 via thetubing 14 and hollow needle 12 and connecting an evacuated collectionvial to the eluate outlet 17 which is in fluid communication with thebottom end 11 of the ion exchange column 7 via the tubing 15 and hollowneedle 13. The pressure differential is established by virtue of thefluid pressure of the saline in the supply vial and the extremely lowpressure in the evacuated collection vial. This urges passage of thesaline solution through the ion exchange column 7 to the collection vialcarrying with it the daughter radioisotope.

As shown in FIG. 2 the hollow spike 22 of the eluent inlet 16 is asingle body 28 which is substantially circular in cross-section and hastwo bores 29, 30 leading to opposed apertures in the sharpened point ofthe spike. The first of the bores 29 is a eluate bore and communicatesdirectly with the outlet fluid connection of the spike which is, inturn, connected to the tubing 14. The second of the two bores 30 is anair bore and leads to a filter chamber 31 and an air hole 32. Althoughthe two apertures in the spike, as illustrated, are both adjacent thetip of the spike, this is not necessary in all cases. The aperture forthe air bore may be located lower down the body of the spike. The filterchamber 31 preferably contains a filter disk 33 of a material suitablefor extracting bacteria from indrawn air such as PTFE(polytetrafluoroethylene) and PVDF (polyvinylidenefluoride).

This construction of fluid inlet ensures that the saline solution can bewithdrawn from the vial without air, which is necessary to equalize thepressure within the vial, entering the fluid flow. More importantly, asa single spike of substantially circular cross-section is employed topenetrate the seal of the saline vial, rotational movement of the vialwithin the well 27 does not result in tearing or other damage to theseal which might permit the ingress of unfiltered air and a breach ofthe aseptic conditions under which the radioisotope is harvested.

Thus, the embodiment of the radioisotope generator described above,provides a more reliable and effective device for the collection ofradioisotopes under aseptic conditions. Further and alternative featuresof the radioisotope generator and of the process of construction of thegenerator are envisaged without departing from the scope of the presentinvention as claimed in the appended claims.

1. A device for producing a fluid containing a radioactive constituent,the device comprising: a shielded chamber within which is located anisotope container housing a radioactive isotope, the shielded chamberincluding first and second fluid connections to opposing ends of theisotope container and a fluid conduit extending from each of the firstand second fluid connections to a fluid inlet and a fluid outletrespectively characterised in that the fluid inlet comprises a singlespike having a substantially circular cross-section, the spike beingadapted to penetrate the rubber seal of a vial and the spike having twobores, the first bore extending from a first aperture adjacent the tipof the spike to a fluid connection with the fluid conduit and the secondbore extending from a second, separate aperture in the spike to afiltering air inlet.
 2. A device as claimed in claim 1 furthercomprising an outer housing which supports the fluid inlet and the fluidoutlet and the spike of the fluid inlet projects through an aperture inthe outer housing.
 3. A device as claimed in claim 2, wherein the outerhousing defines a well about the aperture through which the spikeprojects, the well being structured to receive a vial.
 4. A device asclaimed in claim 1, wherein the filtering air inlet contains a filterdisk of polytetrafluoroethylene.